Project Summary. Each year in the United States, over 300,000 preterm infants are admitted to neonatal intensive care units (NICUs) where they are exposed to a chemical-intensive hospital environment. Many life- saving and supportive respiratory, nutritional, hematologic and pharmaceutical therapies in the NICU expose preterm infants to potentially harmful chemicals during a life stage analogous to the third trimester of gestation. Studies in term-born infants and animal models demonstrate that third trimester in utero exposure to phthalates ?ubiquitous chemicals used to make plastics flexible - is associated with maladaptive neurodevelopmental, pulmonary, reproductive, and growth phenotypes. Lead (Pb) and manganese (Mn) -- an essential trace metal administered in NICU nutrition -- can be neurotoxic in excess resulting in both cognitive and motor deficits. Non-chemical exposures including psychological stress, common in the NICU environment, are also associated with abnormal neurodevelopment. Multiple environmental exposures during the sensitive developmental period when preterm infants are in the NICU may contribute to their increased risk of adverse health and behavioral outcomes later in life. Neither the individual contribution of NICU-based phthalate, Mn, Pb or stress exposure, nor the impact of concurrent and subsequent exposures on preterm infant health, risk, resilience, or disease trajectories have been explored previously. Our research capitalizes on the infrastructure, biorepositories, and extensive clinical databases of four existing preterm cohorts to explore the scientific premise that early life exposure to phthalates, metals, and stress adversely impacts neurodevelopment, lung function, growth and adiposity, and pubertal development in childhood. As part of the ECHO Pediatric Cohorts program, we will pursue the following three specific aims: Aim 1. Identify specific sources of NICU-based phthalate exposure in a large, geographically diverse population of preterm infants. Aim 1 (UG3) will use existing NICU datasets and biorepositories to determine specific routes and sources of phthalate exposure. Aim 2. Measure the impact of NICU-based phthalate exposure on multisystem health outcomes at ages 3-10. Aim 2 (UG3/UH3) examines associations among urine biomarkers of NICU phthalate exposure and childhood measures of pulmonary function, cognitive, motor, and behavioral performance, growth and pubertal development. Aim 3. Determine the impact of and interactions among early childhood phthalate, manganese, lead and stress exposures on neurodevelopmental outcomes in preterm and term children. Aim 3 (UH3) uses tooth, hair and saliva biomarkers of exposures to investigate neurobehavioral development in children born preterm and at term. Our unique cohort offers a windowfor direct measurement of exposures in the ?third trimester? phase of rapid development in a sensitive population. This study will facilitate exposure abatement in the NICU and provide information relevant to fetal and early childhood development.